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Spinocerebellar ataxia type 3
Spinocerebellar ataxia type 3 (SCA3) is a progressive movement disorder characterized by coordination problems, muscle stiffness, and neurological decline.
Overview
Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is a condition involving progressive movement difficulties. It is considered the most common type of spinocerebellar ataxia, though all types are relatively rare. Symptoms typically begin in mid-adulthood, though they can appear from childhood to late adulthood.
Symptoms
Initial signs often include problems with coordination and balance (ataxia). Other symptoms include:
- Speech difficulties
- Uncontrolled muscle tensing (dystonia)
- Muscle stiffness (spasticity) and rigidity
- Tremors
- Bulging eyes and double vision
- Sleep disorders, such as restless leg syndrome or REM sleep behavior disorder
- Peripheral neuropathy (loss of sensation and limb weakness)
- Muscle cramps and twitches (fasciculations)
- Swallowing difficulties
- Cognitive issues involving memory, planning, and problem-solving
Causes
Mutations in the ATXN3 gene cause SCA3. This gene produces the enzyme ataxin-3, which helps remove ubiquitin from proteins tagged for degradation. The mutation involves an expanded CAG trinucleotide repeat. While healthy individuals typically have fewer than 31 repeats, those with SCA3 have more than 50. This expansion leads to an abnormally long, non-functional ataxin-3 enzyme that forms toxic clumps (aggregates) within brain cells, eventually leading to cell death in the brainstem, cerebellum, and spinal cord.
Inheritance
SCA3 is inherited in an autosomal dominant pattern. A phenomenon called anticipation often occurs, where the length of the CAG repeat increases with each generation, typically leading to earlier onset and faster progression of symptoms. This is often more pronounced when inherited from a father.